In this Small Business Innovative Research Phase I project, Los Gatos Research (LGR) proposes to develop and test a novel laser-based spectrophotometer (Water Isotope Analyzer) for measurements of glucose metabolism and of energy expenditure. The instrument will be based on LGR's patented Off-Axis ICOS technology. The Water Isotope Analyzer will be capable of real-time monitoring of H2O isotopes in human and animal blood samples. In this effort, LGR is collaborating with Kinemed Inc. to develop and deploy this inexpensive, portable and fast instrument for measurements of 2H/1H (or D/H) and 18(O)/16(O) in blood samples with a target precision of better than 1 per mil for D/H and 0.4 per mil for 18(O)/16(O). System performance will be demonstrated first in gravimetrically prepared water samples and subsequently in aqueous biological samples. All results will be validated by direct comparison with Isotope Ratio Mass Spectrometry (IRMS) measurements made on the same samples. LGR will develop the instrument and KineMed will provide the test samples and measure them using the IRMS. At the end of Phase I, a prototype system will be made available to a NIA- or CALERIE-designated (Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy) laboratory for evaluation. [unreadable] [unreadable] Project Narrative: LGR's proposed Water Isotope Analyzer will operate autonomously in a clinical setting and report real-time measurements of D/H and 18(O)/16(O) in human blood samples. These new instruments will become the standard methodology for the Doubly-Labeled-Water test for energy expenditure, and for Kinemed's tests for measuring molecular kinetics in living systems, including humans, for metabolic disorders, cancer, and diseases of inflammation and neurodegeneration. The Deuterated Glucose Disposal Test (patented by Kinemed) that Kinemed will initially deploy with LGR's Water Isotope Analyzer involves measurement of glucose metabolism and thus serves as an indicator of insulin resistance. [unreadable] [unreadable] [unreadable]